Fungal infections are difficult to eradicate and can rapidly evolve into invasive and/or systemic disease. These infections require long treatment durations and are associated with high morbidity and mortality, especially in certain populations such as immunocompromised, neonate, and burn patients. Species of Candida are the most common cause of fungal infections, and invasive candidiasis has reported mortality rates of 14-70% (Macherla, C., et al., Front. Microbiol. 2012, 3:193). In addition, interaction of Candida albicans with bacteria in polymicrobial wound infections results in increased virulence compared to monomicrobial infections. Co-infection with Staphylococcus aureus and C. albicans in mice, for instance, causes a synergistic increase in virulence and mortality relative to infection with S. aureus alone. (Hamilton, J. R., et al., Infect. Immun., 1976, 14(4):982-9.)
Fungi are eukaryotes and thus existing antifungal therapeutics may attack similar molecular targets on mammalian cells, resulting in severe side-effects and dosing limitations. Moreover, the formation of biofilms by pathogenic fungal species may result in a significant decrease in susceptibility to conventional antifungal agents. These challenges are exacerbated by the rise of drug resistant Candida species, the limited number of clinically approved antifungals, and the low number of new antifungal drugs in the pipeline for pharmaceutical development. Thus, there currently remains a need for new antifungal agents and methods of treating fungal infections.